2007 Off Campus Research Internship Awardee

Jasmine Shafagh (Biology)
(Concentration in Neural and Behavior Sciences)

Published Paper

Mentor: Dr. Jayasri Das Sarma

(Dept. of Neurology at Jefferson University)

Proposal

Cytokines and Inflammatory diseases, such as MS --- Is there a Link?

Cytokines are secreted proteins that regulate many biological activities, and plays an important role in immunity. A new family of cytokines, IL-17, have been identified and reveal a distinct ligand-receptor signaling system. IL-17 is produced by a sub population of T-cells, Th17 cells. Th17 cells and IL-17 are the major encephalitogenic T cells and cytokines in the EAE. Functional analysis of IL-17 has demonstrated its ability to induce the production of other cytokines and chemokines, such as Il-6, IL-8, G-CSF, GM-CSF, MCP-1 from a variety of cell types. Functional studies have also provided evidence for the importance of IL-17 in the regulation of immune system, its promotion of chronic inflammatory response and Th2 responses. The cognate receptors for the IL-17 family identified thus far are: IL-17R, IL17RH-1. IL-17RL, IL17-RD, and IL-17RE. However, the ligand specificities of many of these receptors have not been established. The IL-17 signaling system is operative in disparate tissues such as articular cartilage, bone, meniscus, brain, hematopoietuc tissue, kidney, skin and intestine. Thus, the evolving IL-17 family of ligands and receptors may play an important role in the homeostasis of tissues in health and disease beyond the immune system. The IL-17 receptor is a Type 1 transmembrane glycoprotein, and shares 84 and 72% aa sequence identity with rat and human IL-17 R (receptor) respectively.

Our research study will be focused to determine the major site of action of IL-17 receptor in the EAE is in the central nervous system (CNS). In other words we will attempt to answer the question: do CNS cells express the IL-17R?

Our research will be as follows:

CNS cells specific localization of IL-17R protein in healthy vs. EAE mice by routine double label immunofluorescence.

Expression of IL-17R mRNA by RT-PCR

Expression of IL-17R protein in neonatal glial cells by Flow cytometry.

Co-culturing of Th1 vs. Th17 cells with neonatal astrocytes/microglia

  • alteration of the expression level of IL-17R

  • functional significance of differential expression and

  • measurement of downstream products (e.g. cytokines, chemokines).
Overall, we expect to verify that the CNS cells do express the IL-17R. Increased understanding of the role of complexity of the cytokine network, together with characterization of its receptor would help to uncover the molecular mechanisms of inflammatory diseases, such as MS.

Program Main Page | Bryn Mawr College | Center for Science in Society | Howard Hughes Medical Institute

These pages are maintained by the Bryn Mawr College Center for Science in Society and Serendip. Send us your comments at Serendip

© by Bryn Mawr College and Serendip 1994-2007 - This Page Last Modified: Wednesday, 5-Oct-2007 11:23:40 EDT